ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Endoplasmic Reticulum Stress Induction and ERK1/2 Activation Contribute to Nefazodone-Induced Toxicity in Hepatic Cells.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- DNAJB4/HLJ1 protects against acetaminophen-induced liver injury by attenuating ER stress via HSP70.Cell biology and toxicology · 2026Article
- 7-Hydroxycannabidiol and 7-carboxycannabidiol induced cytotoxicity via apoptosis and endoplasmic reticulum stress in human hepatic cells.Archives of toxicology · 2025Article
- 4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.Journal of immunology research · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
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- Identifying multiscale translational safety biomarkers using a network-based systems approach.iScience · 2023Article
- Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline.Archives of toxicology · 2022Article
- HiPSC-Derived Hepatocyte-like Cells Can Be Used as a Model for Transcriptomics-Based Study of Chemical Toxicity.Toxics · 2021Article
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- A mechanism of perhexiline's cytotoxicity in hepatic cells involves endoplasmic reticulum stress and p38 signaling pathway.Chemico-biological interactions · 2021Article
- Intermedin facilitates hepatocellular carcinoma cell survival and invasion via ERK1/2-EGR1/DDIT3 signaling cascade.Scientific reports · 2021Article
- Mitochondrial dysfunction and apoptosis underlie the hepatotoxicity of perhexiline.Toxicology in vitro : an international journal published in association with BIBRA · 2020Article
- ATF6 Is a Critical Determinant of CHOP Dynamics during the Unfolded Protein Response.iScience · 2020Article
- Methods for Establishing and Using a Stable Cell Line Expressing Both Gaussia Luciferase and Firefly Luciferase to Screen for Endoplasmic Reticulum Stress.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Role of endoplasmic reticulum stress in depression (Review).Molecular medicine reports · 2019Review
- The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone.Archives of toxicology · 2018Article
- Dynamic imaging of adaptive stress response pathway activation for prediction of drug induced liver injury.Archives of toxicology · 2018Article
- Article
- GlutathioneFrontiers in pharmacology · 2018Article
- Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells.Toxicology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Nefazodone, an antagonist for the 5-hydroxytryptanine receptor, has been used for the treatment of depression. Acute liver injury has been documented to be associated with the use of nefazodone; however, the mechanisms of nefazodone-induced liver toxicity are not well defined. In this report, using biochemical and molecular analyses, we characterized the molecular mechanisms underlying the hepatotoxicity of nefazodone. We found that nefazodone induced endoplasmic reticulum (ER) stress in HepG2 cells, as the expression of typical ER stress markers, including CHOP, ATF-4, and p-eIF2α, was significantly increased, and splicing of XBP1 was observed. Nefazodone-suppressed protein secretion was evaluated using a Gaussia luciferase reporter assay that measures ER stress. The ER stress inhibitors (4-phenylbutyrate and salubrinal) and knockdown of ATF-4 gene attenuated nefazodone-induced ER stress and cytotoxicity. Nefazodone activated the MAPK signaling pathway, as indicated by increased phosphorylation of JNK, ERK1/2, and p38. Inhibition of ERK1/2 reduced ER stress caused by nefazodone. Taken together, our findings suggest that ER stress contributes to nefazodone-induced toxicity in HepG2 cells and that the MAPK signaling pathway plays an important role in ER stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.